P
US7682618B2ExpiredUtilityPatentIndex 85

Generation of virus-like particles and use as panfilovirus vaccine

Assignee: US ARMYPriority: Nov 7, 2001Filed: Apr 13, 2005Granted: Mar 23, 2010
Est. expiryNov 7, 2021(expired)· nominal 20-yr term from priority
Inventors:BAVARI SINAAMAN M JAVADSCHMALJOHN ALAN LWARFIELD KELLY LSWENSON DANA
A61K 39/12C12N 2760/14223A61K 2039/5258C07K 14/005C12N 2810/60C12N 2760/14245C12N 2760/14222C12N 2760/14134C12N 2760/14123C12N 7/00C12N 2760/14234C12N 2760/14145C12N 2760/14122
85
PatentIndex Score
28
Cited by
15
References
58
Claims

Abstract

In this application are described filovirus-like particles for both Ebola and Marburg and their use as a diagnostic and therapeutic agent as well as a filovirus vaccine. Also described is the association of Ebola and Marburg with lipid rafts during assembly and budding, and the requirement of functional rafts for entry of filoviruses into cells.

Claims

exact text as granted — not AI-modified
1. A filovirus virus like particle (VLP) comprising filovirus envelope glycoprotein (GP) and filovirus matrix protein VP40. 
     
     
       2. A filovirus VLP, produced by expressing in a cell a polynucleotide encoding filovirus envelope glycoprotein and filovirus matrix protein VP40 such that said polynucleotide is expressed and said VLP is produced. 
     
     
       3. A VLP of  claim 1  where said filovirus is chosen from the group consisting of Ebola and Marburg. 
     
     
       4. A VLP of  claim 2  where said filovirus is chosen from the group consisting of Ebola and Marburg. 
     
     
       5. A filovirus vaccine comprising VLP according to  claim 1 . 
     
     
       6. A filovirus vaccine comprising VLP according to  claim 2 . 
     
     
       7. A filovirus vaccine according to  claim 6  further comprising an adjuvant. 
     
     
       8. The vaccine of  claim 7  wherein said adjuvant is chosen from the group consisting of: RIBI, QS21 and LT(R192G). 
     
     
       9. A filovirus vaccine according to  claim 5  wherein said filovirus is chosen from the group consisting of Ebola and Marburg. 
     
     
       10. A filovirus vaccine according to  claim 6  wherein said filovirus is chosen from the group consisting of Ebola and Marburg. 
     
     
       11. A filovirus vaccine comprising VLP according to  claim 1  and a nucleic acid encoding an agent capable of eliciting an immune response against said filovirus. 
     
     
       12. An Ebola VLP-producing cell comprising a mammalian cell expressing Ebola GP and VP40. 
     
     
       13. A kit for the detection of Ebola virus infection comprising Ebola VLPs according to  claim 3 . 
     
     
       14. A kit for the detection of Marburg virus infection comprising Marburg VLPs according to  claim 3 . 
     
     
       15. A kit for testing agents involved in Ebola budding said kit comprising a cell producing Ebola VLPs according to  claim 12  and ancillary reagents for detecting VLPs in the supernatant of said cells when cells are cultured. 
     
     
       16. A Marburg VLP-producing cell comprising a mammalian cell expressing Marburg GP and VP40. 
     
     
       17. A kit for testing agents involved in Marburg budding said kit comprising a cell producing Marburg VLPs according to  claim 16  and ancillary reagents for detecting VLPs in the supernatant of said cells when cells are cultured. 
     
     
       18. An immunogenic composition comprising, in a physiologically acceptable vehicle, Ebola VLPs according to  claim 4 . 
     
     
       19. The immunogenic composition according to  claim 18  which further comprises an adjuvant to enhance the immune response. 
     
     
       20. The immunogenic composition of  claim 18 , wherein said Ebola VLPs are produced by expressing in a mammalian cell Ebola GP and Ebola VP40. 
     
     
       21. An immunogenic composition comprising, in a physiologically acceptable vehicle, Marburg VLPs according to  claim 4 . 
     
     
       22. The immunogenic composition according to  claim 21  which induces a Marburg specific immune response in a subject. 
     
     
       23. The immunogenic composition according to  claim 21 , which further comprises an adjuvant to enhance the immune response. 
     
     
       24. The immunogenic composition of  claim 21 , wherein said Marburg VLPs are produced by expressing in a mammalian cell Marburg GP and Marburg VP40. 
     
     
       25. A panfilovirus vaccine comprising a mixture of EBOV and MARV VLPs according to  claim 4 . 
     
     
       26. A MARV vaccine protective against infection with MARV-Musoke, MARV-Ravn, and MARV-Ci67, comprising MARV VLPs according to  claim 4  consisting essentially of GP and VP40 from MARV-Musoke. 
     
     
       27. An Ebola VLP producing cell comprising an insect cell expressing Ebola GP and VP40. 
     
     
       28. A Marburg VLP producing cell comprising an insect cell expressing Marburg GP and VP40. 
     
     
       29. A filovirus virus like particle (VLP) comprising filovirus envelope glycoprotein (GP), filovirus matrix protein VP40, and filovirus nucleoprotein (NP). 
     
     
       30. A filovirus VLP, produced by expressing in a cell a polynucleotide encoding filovirus envelope glycoprotein, filovirus matrix protein VP40, and filovirus nucleoprotein NP, such that said polynucleotide is expressed and said VLP is produced. 
     
     
       31. The filovirus VLP according to  claim 30  wherein said cell is chosen from the group consisting of mammalian cell and insect cell. 
     
     
       32. A VLP of  claim 29  where said filovirus is chosen from the group consisting of Ebola and Marburg. 
     
     
       33. A VLP of  claim 30  where said filovirus is chosen from the group consisting of Ebola and Marburg. 
     
     
       34. A filovirus vaccine comprising VLP according to  claim 29 . 
     
     
       35. A filovirus vaccine comprising VLP according to  claim 30 . 
     
     
       36. A filovirus vaccine according to  claim 34  further comprising an adjuvant. 
     
     
       37. The vaccine of  claim 36  wherein said adjuvant is chosen from the group consisting of: RIBI, QS21 and LT(R192G). 
     
     
       38. A filovirus vaccine according to  claim 34  wherein said filovirus is chosen from the group consisting of Ebola and Marburg. 
     
     
       39. A filovirus vaccine according to  claim 35  wherein said filovirus is chosen from the group consisting of Ebola and Marburg. 
     
     
       40. A filovirus vaccine comprising VLP according to  claim 29  and a nucleic acid encoding an agent capable of eliciting an immune response against said filovirus. 
     
     
       41. An Ebola VLP-producing cell wherein said cell expresses Ebola GP, VP40, and NP. 
     
     
       42. A method for detecting Ebola virus infection comprising contacting a sample from a subject suspected of having Ebola virus infection with an Ebola VLP according to  claim 32  and detecting the presence or absence of an infection by detecting the presence or absence of a complex formed between the Ebola VLP and antibodies specific therefor in said sample. 
     
     
       43. A kit for the detection of Ebola virus infection comprising Ebola VLPs according to  claim 32 . 
     
     
       44. A method for detecting Marburg virus infection comprising contacting a sample from a subject suspected of having Marburg virus infection with a Marburg VLP according to  claim 32  and detecting the presence or absence of an infection by detecting the presence or absence of a complex formed between the Marburg VLP and antibodies specific therefor in said sample. 
     
     
       45. A kit for the detection of Marburg virus infection comprising Marburg VLPs according to  claim 32 . 
     
     
       46. A kit for testing agents involved in Ebola budding said kit comprising a cell producing Ebola VLPs according to  claim 41  and ancillary reagents for detecting VLPs in the supernatant of said cells when cells are cultured. 
     
     
       47. A Marburg VLP-producing cell wherein said cell expresses Marburg GP, VP40, and NP. 
     
     
       48. A kit for testing agents involved in Marburg budding said kit comprising a cell producing Marburg VLPs according to  claim 47  and ancillary reagents for detecting VLPs in the supernatant of said cells when cells are cultured. 
     
     
       49. An immunogenic composition comprising, in a physiologically acceptable vehicle, Ebola VLPs according to  claim 32 . 
     
     
       50. The immunogenic composition according to  claim 49  which further comprises an adjuvant to enhance the immune response. 
     
     
       51. The immunogenic composition of  claim 50 , wherein said Ebola VLPs are produced by expressing in an insect cell Ebola GP, Ebola VP40, and Ebola NP. 
     
     
       52. An immunogenic composition comprising, in a physiologically acceptable vehicle, Marburg VLPs according to  claim 32 . 
     
     
       53. The immunogenic composition according to  claim 52  which induces a Marburg specific immune response in a subject. 
     
     
       54. The immunogenic composition according to  claim 52 , which further comprises an adjuvant to enhance the immune response. 
     
     
       55. The immunogenic composition of  claim 52 , wherein said Marburg VLPs are produced by expressing in an insect cell Marburg GP, Marburg VP40, and Marburg NP. 
     
     
       56. A panfilovirus vaccine comprising a mixture of EBOV and MARV VLPs according to  claim 32 . 
     
     
       57. The immunogenic composition according to  claim 18  which induces an Ebola specific immune response in a subject. 
     
     
       58. The filovirus VLP according to  claim 31  wherein said filovirus is chosen from the group consisting of Ebola and Marburg.

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